7-（Diethylamino）-3-（4-aminophenyl）coumarin has been synthesized in a new one-pot synthesis by a three-step process starting from 4-（diethylamino）salicylaldehyde and 4-nitrophenylacetonitrile. The product was obt...7-（Diethylamino）-3-（4-aminophenyl）coumarin has been synthesized in a new one-pot synthesis by a three-step process starting from 4-（diethylamino）salicylaldehyde and 4-nitrophenylacetonitrile. The product was obtained in a good yield with a high degree of purity and characterized by NMR, IR and HR-MS. The orange crystals of the title compound were grown from ethyl acetate solution. The solid state structure was established by X-ray crystallography analysis. The crystal belongs to the orthorombic system, space group Pccn with a = 11.1095（5）, b = 33.0187（15）, c = 17.2865（7） A, V= 6341.1（5） A3, C19H20N2O2, Mr = 308.37, ρcalc = 1.292 g·cm^-3, = 0.085 mm^-1, F（000） = 2624, the final R = 0.0480 and wR = 0.1265 （I〉 2σ（I））.展开更多
Levothyroxine is a drug with a narrow therapeutic index.Changing the drug formulation composition or switching between pharmaceutical brands can alter the bioavailability,which can result in major health problems.Howe...Levothyroxine is a drug with a narrow therapeutic index.Changing the drug formulation composition or switching between pharmaceutical brands can alter the bioavailability,which can result in major health problems.However,the increased adverse drug reactions have not been fully explained scientifically yet and a thorough investigation of the formulations is needed.In this study,we used a non-targeted analytical approach to examine the various levothyroxine formulations in detail and to reveal possible chemical changes.Ultra-high-performance liquid chromatography coupled with a data-independent acquisition high-resolution mass spectrometry(UHPLC-DIA-HRMS)was employed.UHPLC-DIA-HRMS allowed not only the detection of levothyroxine degradation products,but also the presence of non-expected components in the formulations.Among these,we identified compounds resulting from reactions between mannitol and other excipients,such as citric acid,stearate,and palmitate,or from reactions between an excipient and an active pharmaceutical ingredient,such as levothyroxine-lactose adduct.In addition to these compounds,undeclared phospholipids were also found in three formulations.This non-targeted approach is not common in pharmaceutical quality control analysis.Revealing the presence of unexpected compounds in drug formulations proved that the current control mechanisms do not have to cover the full complexity of pharmaceutical formulations necessarily.展开更多
Ionic liquids are green solvents with interesting properties:displaying low melting points and high boiling points.They offer a new approach applicable in many instances.Nevertheless,the presence of free ions can be a...Ionic liquids are green solvents with interesting properties:displaying low melting points and high boiling points.They offer a new approach applicable in many instances.Nevertheless,the presence of free ions can be a matter in some cases,e.g.for the study of nucleophilic reactions,in electrochemistry,and in each situation where there is a competition between counter ions,as in micellization of ionic surfactants.Neutral compounds having formal unit electrical charges of opposite sign,and the same physical properties than ionic liquids would be a nice alternative to these latter solvents.There are two classes of chemical compounds having these characteristics:zwitterionic liquids(with no uncharged canonical representation) and mesoionic liquids(in which the negative and the positive charges are delocalized).In that last class we have chosen to work with 3-methylsydnone in order to examine,in this aprotic solvent,if it was possible to observe aggregation of surfactants in the same manner as in water.With all kinds of surfactants studied(ionic,zwitterionic and mesoionic) we have been able to demonstrate the formation of direct micelles:hydrogen bonding is thus not mandatory for molecular aggregation.Comparison of the behavior in water and in formamide showed that solvophobic interactions were qualitatively comparable but with a lower intensity.展开更多
基金The"Groupement Franco-Ukrainien en Chimie Moléculaire"(GDRI)and the Embassy of France in Kyiv are gratefully acknowledged for financial support
文摘7-（Diethylamino）-3-（4-aminophenyl）coumarin has been synthesized in a new one-pot synthesis by a three-step process starting from 4-（diethylamino）salicylaldehyde and 4-nitrophenylacetonitrile. The product was obtained in a good yield with a high degree of purity and characterized by NMR, IR and HR-MS. The orange crystals of the title compound were grown from ethyl acetate solution. The solid state structure was established by X-ray crystallography analysis. The crystal belongs to the orthorombic system, space group Pccn with a = 11.1095（5）, b = 33.0187（15）, c = 17.2865（7） A, V= 6341.1（5） A3, C19H20N2O2, Mr = 308.37, ρcalc = 1.292 g·cm^-3, = 0.085 mm^-1, F（000） = 2624, the final R = 0.0480 and wR = 0.1265 （I〉 2σ（I））.
基金supported by the project EFSA-CDN(Project No.:CZ.02.01/0.0/0.0/16_019/0000841)co-funded by ERDF.
文摘Levothyroxine is a drug with a narrow therapeutic index.Changing the drug formulation composition or switching between pharmaceutical brands can alter the bioavailability,which can result in major health problems.However,the increased adverse drug reactions have not been fully explained scientifically yet and a thorough investigation of the formulations is needed.In this study,we used a non-targeted analytical approach to examine the various levothyroxine formulations in detail and to reveal possible chemical changes.Ultra-high-performance liquid chromatography coupled with a data-independent acquisition high-resolution mass spectrometry(UHPLC-DIA-HRMS)was employed.UHPLC-DIA-HRMS allowed not only the detection of levothyroxine degradation products,but also the presence of non-expected components in the formulations.Among these,we identified compounds resulting from reactions between mannitol and other excipients,such as citric acid,stearate,and palmitate,or from reactions between an excipient and an active pharmaceutical ingredient,such as levothyroxine-lactose adduct.In addition to these compounds,undeclared phospholipids were also found in three formulations.This non-targeted approach is not common in pharmaceutical quality control analysis.Revealing the presence of unexpected compounds in drug formulations proved that the current control mechanisms do not have to cover the full complexity of pharmaceutical formulations necessarily.
文摘Ionic liquids are green solvents with interesting properties:displaying low melting points and high boiling points.They offer a new approach applicable in many instances.Nevertheless,the presence of free ions can be a matter in some cases,e.g.for the study of nucleophilic reactions,in electrochemistry,and in each situation where there is a competition between counter ions,as in micellization of ionic surfactants.Neutral compounds having formal unit electrical charges of opposite sign,and the same physical properties than ionic liquids would be a nice alternative to these latter solvents.There are two classes of chemical compounds having these characteristics:zwitterionic liquids(with no uncharged canonical representation) and mesoionic liquids(in which the negative and the positive charges are delocalized).In that last class we have chosen to work with 3-methylsydnone in order to examine,in this aprotic solvent,if it was possible to observe aggregation of surfactants in the same manner as in water.With all kinds of surfactants studied(ionic,zwitterionic and mesoionic) we have been able to demonstrate the formation of direct micelles:hydrogen bonding is thus not mandatory for molecular aggregation.Comparison of the behavior in water and in formamide showed that solvophobic interactions were qualitatively comparable but with a lower intensity.
